Something Wicked This Way Comes

The 20th century is often portrayed as an era in which American
medicine triumphed over infectious disease. In 1900, pneumonia,
tuberculosis, diarrhea and enteritis, and diphtheria together
accounted for about a third of U.S. deaths. Today, Americans are
usually killed by chronic conditions that afflict us in our later
years, such as heart disease and cancer. This summary, however,
conceals two darker truths. First, despite the overall decline in
infectious disease over the past century, there have been some
dramatic disease outbreaks, most notably the 1918 flu pandemic and
the current HIV epidemic. Second, much of the developing world (Cuba
and Costa Rica are notable exceptions) has yet to make the
transition away from infectious diseases as the leading causes of
death. Such diseases are a harsh and daily reality for most of humanity.

Now the dangers of the new H5N1 influenza strain are entering the
public's consciousness. As sound bites and headlines proclaim that
an avian flu pandemic is imminent, thoughtful and measured analysis,
and context, are needed. Mike Davis's new book, The Monster at
Our Door, offers just that. Davis, an engrossing writer,
provides a useful introduction to the biology of the influenza virus
and to its many devious evolutionary tricks.

The book's main strength, however, stems from the skill with which
Davis has documented the many ways in which human greed, folly and
political ambition threaten our ability to respond effectively to
this latest emerging infectious disease. He consistently makes
unexpected connections. His account, for instance, of the rise of
industrialized poultry farming in China and Thailand, driven by the
increased demand for meat in Asia, both rivets and disturbs. He
details how small farmers raising flocks of chickens, ducks and
geese have been replaced by immense industrial conglomerates that
crowd hundreds of thousands of birds in close proximity. The
epidemiological implications of this transition are devastating.
Previously, an infectious outbreak would be largely self-limiting,
racing through a small flock and then flaming out. Now, however,
conditions exist for extensive outbreaks that can quickly infect
huge numbers of birds. They—and their droppings—act as
sources of infection for other domesticated and wild birds. Many of
the susceptible wild fowl are part of the annual migratory cycles
that girdle the planet. As a result, the initial outbreaks of bird
flu reported in late 2004 in Vietnam and China have quickly made
their way to Siberia, Turkey and now Eastern Europe through the
Danube Delta.

As Davis points out, the concentration of economic power and
influence in huge poultry conglomerates militates against a rapid
and rational response to outbreaks of bird flu. In chilling detail,
The Monster at Our Door exposes the political pressures
exerted on the government of Thailand by Charoen Pokphand (CP), the
country's dominant poultry concern. These pressures have slowed the
reporting of avian influenza, obstructed the monitoring of chicken
and duck facilities, and limited efforts to cull infected flocks in
order to prevent the spread of disease. They have also redirected
the government's control measures onto the few remaining small
farmers who raise chickens, often forcing them out of business and
thus further tightening CP's food monopoly in Thailand. (This story
of political corruption and influence is not without its
surrealistic touches: In 2004, the Thai ambassador to Moscow offered
to barter 250,000 tons of Thai chicken—the shipment would have
begun with 60,000 tons of chicken possibly contaminated with
H5N1—in exchange for Russian Sukhoi Su-30 fighter aircraft.
The offer was declined.)

The Monster at Our Door emphasizes that epidemics are rare
episodes in which the delicate minuet between infectious agents and
their potential hosts breaks down. If we want to understand the
causes of epidemics—surely a prelude to preventing or
controlling them—we must look to the ecology of hosts, vectors
and agents in the broadest sense. In the case of human epidemics,
that means understanding not only the ways in which the immune
system sees and tracks the influenza virus but also the forces that
have given rise to, say, Brazilian slums, or large-scale
agribusiness in the developing world.

This broader perspective forces us to acknowledge that potentially
effective antiviral agents such as Tamiflu will be of little help,
given that 95 percent of the world does not have access to them. In
the event that there is a worldwide influenza pandemic, Davis
convincingly argues, the workings of the free market are not likely
to result in optimum allocation of effort or resources. He makes
this case methodically, following the money and the political
ambitions that complicate our understanding of this disease and its
prevention. The tone throughout is urgent but not shrill, and the
book's bibliography underscores the careful research underlying
Davis's arguments.

So how scared should we be? The answer is not obvious, and Davis's
conclusions are necessarily speculative. The influenza virus is a
formidable adversary, with a set of fiendish molecular tricks in its
arsenal. Like many viruses, it has evolved replication machinery
that is sloppy (unlike ours, which is uncannily accurate). This
sloppiness translates into myriad versions of the viral genetic
blueprint being passed on to successive generations. But there is
method to this seeming madness: Each of these variants encodes a
slightly different version of the virus's surface proteins. Because
the immune system of a host—a chicken, an egret or a
person—works primarily by recognizing the shape of the
proteins on the surface of the virus, sloppy viral replication
allows influenza to evade the scrutiny of the immune system. This
process, antigenic drift, is akin to convicts on the lam shaving
their hair or growing mustaches to keep one step ahead of the law.

But the influenza virus, by virtue of having a genome that comes in
eight pieces, has an even more fiendish trick, comparable to
undergoing plastic surgery: By borrowing a genome fragment from an
unrelated strain, the virus can make itself virtually unrecognizable
to the immune system of the host. This strategy, antigenic shift,
results in a new, previously unseen type of influenza virus.

The H5N1 strain now causing concern worldwide is present in
domesticated and wild birds and has seldom been seen in the human
population. Thus exposure to, or vaccination against, previous
strains of flu confers no protection against it. The current H5N1
strain is also unusually virulent, with mortality rates approaching
50 percent. But neither its novelty nor its virulence guarantees an
epidemic. So far, H5N1 does not appear to have cracked the code for
human-to-human transmission; all but a few cases are clearly the
result of bird-to-human transmission. But how many mutations away is
the virus from acquiring the ability to move from one person to another?

Davis points out that previous epidemics offer tantalizing but
inconclusive clues to the answer. The recently reconstituted genome
of the 1918 strain bears a troubling resemblance to the genome of
the current H5N1 strain, although it also differs subtly from H5N1
at virtually every gene. The keys to the lethality and
transmissibility of the 1918 strain lie somewhere in those
differences. But no single genetic change appears to turn an
ordinary flu strain into a lethal killer. We can take some small
measure of comfort from the fact that multiple mutations must be
present simultaneously to set the conditions for a human pandemic.

We know little about the evolutionary trajectory that results in
human-to-human transmission. Genetic changes may have to occur in a
specific order for the virus to survive every step of its
metamorphosis into an aggressive killer. But the specter looms in
the background that in one fell swoop H5N1 could undergo antigenic
shift: It could acquire a genomic fragment from a strain already
adapted for survival and movement in a human host and be effectively
catapulted into the role of widespread killer.

Davis does an exemplary job of guiding readers through the
intricacies of viral genetics, but he reminds us that the molecular
basis of virulence and transmissibility is but one part of the
story. We can do little to control the evolutionary excursions of
the influenza genome, but we can alter the human ecology
that makes pandemics possible. The Monster at Our Door is a
call for human solidarity and for the internationalization of
monitoring and prevention efforts.

As Davis emphasizes, the notion that the influenza pandemic can be
stopped at our country's borders and the belief that American
medicine is a sufficient bulwark against such a threat are
unsupportable. Ultimately, the irony of the early 21st century could
turn out to be the return of infectious diseases, old and new, as
the prevailing threats to human survival. It will take what is best
in our species—solidarity, inventiveness and
cooperation—to keep the past from becoming the future.